The molybdenum cofactor consists, inter alia, of a pterin component termed molybdopterin complexed with molybdenum. It appears to be a universal cofactor for a wide variety of molybdenum-containing enzymes, acting as a link to bind the enzyme subunits to form an active enzyme, and functioning as an electron carrier. Human genetic deficiency in cofactor synthesis is a condition characterized by severe neuropathy and early death. Furthermore, the recent finding that some 5% of all asthmatics are sensitive to SO2 and bisulfite suggests that these susceptible individuals might have a deficiency of sulfite oxidase, and enzyme totally dependent on the molybdenum cofactor for its activity. It is the aim of this proposal to develop unequivocal synthetic approaches to molybdopterin its biosynthetic precursor(s), and to the cofactor itself. This work will provide critical structural and stereochemical information on molybdopterin, and will make possible a study of the possible therapeutic utility of synthetic molybdenum cofactor.